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Phage therapy for intracellular pathogens

Westmead Institute for Medical Research and University of Sydney

Grant:
  • PhD Scholarship
Date Funded:
  • 17 May, 2021
Chief Investigator/s:
  • Professor Jon Iredell

Research intent

Development of phage – antibiotic combinations that effectively kill diarrhoeal pathogens (e.g., Shigella, Salmonella) inside mammalian cells.

What is the issue?

Shigella is the most severe of the bacterial diarrhoeal pathogens and the best example for the problem in NSW. It is a leading cause of childhood mortality around the world and has become extremely resistant (XDR) to antibiotic. This is a great threat to children, especially in our Aboriginal and CALD communities. New therapies are urgently needed as all our antibiotics are failing. Shigella is an archetype for all enteroinvasive bacterial pathogens and lessons learnt here will be broadly informative and applied to other intracellular enteric pathogens (such as Salmonella or invasive E. coli).

What does the research aim to do and how?

We will define the most potent bacteriophage cocktails, in combination with antibiotics, against three major enteric intracellular pathogens (Shigella, Salmonella and invasive E. coli). This project will include bacterial population analysis (genomics) and phage characterization (genomics, microscopy, phage stability assays), analysis of phage-bacteria dynamics in vitro and ex vivo (inside eukaryotic cells) and phage purification. We will make these combinations available for therapy where current antibiotics fail. The student will learn all the processes required to take this therapy through to completion.